红景天苷衍生物S01对谷氨酸及缺氧缺糖所致SH-SY5Y细胞损伤的保护作用

目的探讨红景天苷衍生物S01(3′,4′,5′-三甲氧基苄基-1-硫代-β-D-吡喃葡萄糖苷)对神经细胞的保护作用,并初步探讨其作用机制。方法用不同浓度S01(2,10和50mg.L-1)预处理SH-SY5Y细胞,12h后用谷氨酸或连二亚硫酸钠(Na2S2O4)诱导SH-SY5Y细胞损伤,用MTT法检测细胞存活率,比色法检测乳酸脱氢酶(LDH)释放、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,荧光探针负载法检测细胞内活性氧(ROS)水平和细胞内游离钙离子浓度([Ca2+]i),化学发光法检测细胞中腺苷三磷酸(ATP)水平。结果在谷氨酸所致SH-SY5Y细胞损伤模型中,与对照组比较,模型组细胞存活率、SOD活性和ATP水平降低,LDH释放、MDA含量和细胞内ROS水平增加。与模型组比较,S01(2,10和50mg.L-1)可提高细胞存活率,减少谷氨酸引起的LDH释放,拮抗谷氨酸引起的SOD活性和ATP水平降低,并拮抗MDA和ROS水平升高。在Na2S2O4所致SH-SY5Y细胞缺氧缺糖损伤模型中,与对照组比较,模型组细胞存活率下降,LDH释放增多,细胞[Ca2+]i升高。与模型组比较,S01(2,10和50mg.L-1)可提高细胞存活率,减少缺氧缺糖引起的LDH释放和细胞内钙超载。结论S01对谷氨酸和缺氧缺糖所致神经细胞损伤具有保护作用,提示S01可能对脑缺血具有治疗作用。

Protection of rhodioside derivative S01 against damage of SH-SY5Y cells induced by glutamate and oxygen-glucose deprivation

AIM To study the neuroprotective effect of rhodioside derivative S01 (3′,4′,5′-trimethoxybenzyl-1-thio-β-D-glucopyranoside) on neural cells and its related mechanism. METHODS SH-SY5Y cells were pretreated with S01 (2, 10 and 50 mg·L^-1, respectively) 12 h and then induced damage by glutamate or oxygen-glucose deprivation. The cell survival rate was detected by using MTT. Lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected by colorimetry. Intracellular reactive oxygen species (ROS) level and free Ca^2＋ concentration (［Ca^2＋］_i) were detected with fluorescence probe, and adenosine triphosphate (ATP) level was detected by using luminometer. RESULTS In glutamate-induced SH-SY5Y cell damage model, compared with control group, the cell survival rate, SOD activity and ATP level were decreased, while LDH release, and MDA and ROS levels were increased. Compared with glutamate group, S01 (2, 10 and 50 mg·L^-1) elevated the cell survival rate, but reduced LDH release induced by glutamate. Furthermore, S01 inhibited the decrease in SOD activity and ATP level, and the increase in MDA level. In Na₂S₂O₄-induced oxygen-glucose deprivation damage cell model, compared with control group, the cell survival rate decreased, while LDH release and ［Ca^2＋］_i increased, which were attenuated by S01 (2, 10 and 50 mg·L^-1). CONCLUSION S01 can protect neuron-like cells from the damage induced by glutamate and oxygen-glucose deprivation, which indicates that S01 may have the potential to treat cerebral ischemia.